3-12379784-G-T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP2
The NM_138711.6(PPARG):c.73G>T(p.Asp25Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D25N) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Consequence
PPARG
NM_138711.6 missense
NM_138711.6 missense
Scores
3
9
7
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 8.99
Publications
0 publications found
Genes affected
PPARG (HGNC:9236): (peroxisome proliferator activated receptor gamma) This gene encodes a member of the peroxisome proliferator-activated receptor (PPAR) subfamily of nuclear receptors. PPARs form heterodimers with retinoid X receptors (RXRs) and these heterodimers regulate transcription of various genes. Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of adipocyte differentiation. Additionally, PPAR-gamma has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis and cancer. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2008]
PPARG Gene-Disease associations (from GenCC):
- PPARG-related familial partial lipodystrophyInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P, Genomics England PanelApp
- Berardinelli-Seip congenital lipodystrophyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the PPARG gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 16 curated pathogenic missense variants (we use a threshold of 10). The gene has 5 curated benign missense variants. Gene score misZ: 2.1192 (below the threshold of 3.09). Trascript score misZ: 3.0978 (above the threshold of 3.09). GenCC associations: The gene is linked to PPARG-related familial partial lipodystrophy, Berardinelli-Seip congenital lipodystrophy.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.;.;.;.;.;.;T;T;T;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;.;.;.;.;.;.;.;D;.;.;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;.;.;.;.;.;.;.;.;.;.;L
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;.;.;.;D;N;N;D;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;.;.;.;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;.;.;.;D;D;D;D;D;D
Polyphen
0.98
.;.;.;.;.;.;.;.;.;.;.;D;D
Vest4
MutPred
0.48
.;.;.;.;.;.;.;.;.;.;.;.;Loss of disorder (P = 0.0168);
MVP
MPC
0.62
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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